Regulation of eating habits

ABSTRACT

A method for treating a subject is provided, including receiving a sensor signal responsive to the subject eating, analyzing the sensor signal, and driving a current into tissue of the subject responsive to analyzing the signal. The current is typically driven into muscle tissue of the subject&#39;s stomach ( 20 ). Preferably, receiving the sensor signal includes sensing electrical potential change generated responsive to contraction of a muscle such as a stomach muscle of the subject. In a preferred embodiment, the sensor signal is analyzed with respect to the timing of ingestion, and a level of compliance of the subject with a desired ingestion schedule is determined. As appropriate, a parameter of the current driven into the tissue may be configured such that the application of the current to the tissue induces in the subject a sensation of satiation, discomfort, nausea, or vertigo.

FIELD OF TIE INVENTION

[0001] The present invention relates generally to appetite regulation,and specifically to invasive techniques and apparatus for appetitecontrol and treating obesity.

BACKGROUND OF THE INVENTION

[0002] Morbid obesity is a difficult to treat chronic condition definedby a body mass index (BMI=mass/height²[kg/m²]) greater than 40. Forobese persons, excessive weight is commonly associated with increasedrisk of cardiovascular disease, diabetes, degenerative arthritis,endocrine and pulmonary abnormalities, gallbladder disease andhypertension. Additionally, such persons are highly likely to experiencepsychological difficulties because of lifestyle restrictions such asreduced mobility and physical capacity, due to back pain, jointproblems, and shortness of breath. In severe cases, this can contributeto absenteeism and unemployment. Moreover, impairment of body image canlead to significant psychological disturbances. Repeated failures ofdieting and exercise to resolve the problem of obesity can result infeelings of despair and the development of clinical depression.

[0003] Bariatric surgery is often recommended for persons suffering frommorbid obesity. Preferably, the invasive treatment is accompanied bychanges in lifestyle, such as improved regulation of eating habits andan appropriate exercise regimen. Such lifestyle changes are dependentupon the self-discipline and cooperation of the patient.

[0004] A book entitled, Textbook of Gastroenterology, 3rd edition,edited by Yamada (Lippincott, Williams & Wilkns), which is incorporatedherein by reference, has in Chapter 10 thereof, a description of thephysiology of gastric motility and gastric emptying.

[0005] An abstract entitled, “Gastric myoelectrical pacing as therapyfor morbid obesity: Preliminary results,” by Cigaina et al., retrievedon Dec. 24, 2000 from the Web-sitehttp://www.med-online.com/transneuronix/Product/abstract.htm, which isincorporated herein by reference, describes a method for applyingmonopolar and bipolar gastric stimulation to achieve weight loss.

[0006] An abstract entitled, “implantable gastric stimulator (IGS) astherapy for morbid obesity: Equipment, surgical technique andstimulation parameters,” by Cigaina et al., retrieved on Dec. 24, 2000from the Web-sitehttp://www.med-online.com/transneuronix/Product/abstract.htm, which isincorporated herein by reference, describes techniques of electricalsignal therapy designed to treat obesity.

[0007] U.S. Pat. No. 6,129,685 to Howard, which is incorporated hereinby reference, describes apparatus and methods for regulating appetite byelectrical stimulation of the hypothalamus and by microinfusion of anappropriate quantity of a suitable drug to a distinct site or regionwithin the hypothalamus.

[0008] U.S. Pat. No. 4,823,808 to Clegg et al., which is incorporatedherein by reference, describes a method for treating obesity, includingreceiving a physiological measurement and generating audio and/or visualfeedback for the patient to hear and/or see. The feedback is used forpurposes of teaching behavior modification.

[0009] U.S. Pat. No. 5,868,141 to Ellias, which is incorporated hereinby reference, describes an endoscopic stomach insert for reducing apatient's desire to eat.

[0010] U.S. Pat. No. 6,067,991 to Forsell, U.S. Pat. No. 5,601,604 toVincent, U.S. Pat. No. 5,234,454 to Bangs, U.S. Pat. No. 4,133,315 toBerman et al., U.S. Pat. No. 4,416,267 to Garren et al., and U.S. Pat.Nos. 4,592,339, 5,449,368, 5,226,429 and 5,074,868 to Kuzmak, which areincorporated herein by reference, describe mechanical instruments forimplantation in or around the stomach of an obese patient.

[0011] U.S. Pat. No. 5,690,691 to Chen et al., which is incorporatedherein by reference, describes a gastric pacemaker for treating obesityand other disorders. The pacemaker includes multiple electrodes whichare placed at various positions on the gastrointestinal (GI) tract, anddeliver phased electrical stimulation to pace peristaltic movement ofmaterial through the GI tract.

[0012] U.S. Pat. No. 5,423,872 to Cigaina, which is incorporated hereinby reference, describes apparatus for applying electrical pulses to thedistal gastric antrum of a patient, so as to reduce the motility of thestomach and to thereby treat obesity or another disorder.

[0013] U.S. Pat. Nos. 5,188,104 and 5,263,480 to Wernicke et al., whichare incorporated herein by reference, describe a method for stimulatingthe vagus nerve of a patient so as to alleviate an eating disorder.

[0014] U.S. Pat. Nos. 6,104,955, 6,091,992, and 5,836,994 to Bourgeois,U.S. Pat. No. 6,026,326 to Bardy, and U.S. Pat. No. 3,411,507 toWingrove, which are incorporated herein by reference, describe theapplication of electrical signals to the GI tract to treat variousphysiological disorders.

[0015] U.S. Pat. No. 5,979,449 to Steer, which is incorporated herein byreference, describes an oral appliance for appetite suppression.

[0016] U.S. Pat. No. 4,975,682 to Kerr et al., which is incorporatedherein by reference, describes apparatus for food intake regulationwhich is external to the body and which is based upon the voluntarycooperation of the subject in order to be effective.

[0017] U.S. Pat. Nos. 5,861,014, 5,716,385 and 5,995,872 areincorporated herein by reference, and describe methods and apparatus forstimulation of tissue, particularly gastrointestinal tract tissue.

[0018] PCT Patent Publication WO 98/10830 to Ben-Haim et al., entitled,“Fencing of cardiac muscles,” and U.S. patent application Ser. No.09/254,903 in the national phase thereof, both of which are assigned tothe assignee of the present patent application and are incorporatedherein by reference, describe various methods for controlling thebehavior of muscle tissue, for example by blocking or altering thetransmission of signals therethrough.

[0019] PCT Patent Publication WO 99/03533 to Ben-Haim et al., entitled,“Smooth muscle controller,” and U.S. patent application Ser. No.09/481,253 in the national phase thereof, both of which are assigned tothe assignee of the present patent application and are incorporatedherein by reference, describe apparatus and methods for applying signalsto smooth muscle so as to modify the behavior thereof. In particular,apparatus for controlling the stomach is described in which a controllerapplies an electrical field to electrodes on the stomach wall so as tomodify the reaction of muscle tissue therein to an activation signal,while not generating a propagating action potential in the tissue. Inthe context of the present patent application and in the claims, the useof such a non-excitatory signal to modify the response of one or morecells to electrical activation thereof, without inducing actionpotentials in the cells, is referred to as Excitable-Tissue Control(ETC). Use of an ETC signal is described with respect to treatingobesity, by applying the ETC signal to the stomach so as to delay orprevent emptying of the stomach. In addition, a method is described forincreasing the motility of the gastrointestinal tract, by applying anETC signal to a portion of the tract in order to increase thecontraction force generated in the portion and the stretching of nearbytissue.

SUMMARY OF THE INVENTION

[0020] It is an object of some aspects of the present invention toprovide apparatus and methods for regulation of appetite and foodingestion.

[0021] It is a further object of some aspects of the present inventionto provide improved apparatus and methods for treating obesity.

[0022] It is yet a further object of some aspects of the presentinvention to provide apparatus and methods that enable change in foodingestion habits in a predictable and controlled manner.

[0023] It is still a further object of some aspects of the presentinvention to provide apparatus and methods for bariatric surgery whichare less drastic than those currently employed.

[0024] In preferred embodiments of the present invention, apparatus forregulating a patient's food ingestion comprises a sensor which detects:(a) the patient swallowing, (b) the filling of the patient's stomach,and/or (c) the onset of contractions in the stomach as a result ofeating. Preferably, a timing module stores in an electronic memory thetime of each swallow and/or meal. Additionally or alternatively, ameasuring module stores in the memory the amount of food consumed in themeal. Further additionally or alternatively, the measuring moduledetermines a quality of the food, for example whether it ispredominantly solid or liquid. For most applications, a specificschedule of allowed food ingestion is pre-programmed by a physician intothe memory, and a processor is continuously operative to detect whetherfood consumption is taking place in accordance with the programmedschedule. For some patients, the schedule may be less strict withrespect to the drinking of liquids, and more strict with respect to theeating of solid food. When an exception from the schedule is detected,the processor actuates a signal generator to convey an ingestion-controlsignal to the patient, in order to encourage the patient to adhere tothe schedule.

[0025] Typically, the ingestion-control signal is delivered to thepatient's stomach via a set of electrodes placed in a vicinity thereof,so as to induce a sensation of satiety, discomfort, or minor nauseaThus, for example, in response to detecting a violation of the patient'sprescribed diet and/or eating schedule, the processor may drive thesignal generator to induce an unpleasant sensation (e.g., nausea) byaltering the natural electrical activity of the stomach, therebyinducing gastric dysrhythmia. For some applications, the signal isapplied to another site on or in the patient's body. For example, theingestion-control signal may be applied mechanically or electrically ina vicinity of the cochlear nerve, so as to induce vertigo. Alternativelyor additionally, the signal is applied so as to generate a brief painsensation anywhere on the patient's body, which only recurs if thepatient continues to eat.

[0026] Preferably, but not necessarily, the measuring module determinesthe quality of the food (e.g., solid or liquid) by interpretingelectrical signals generated in the gastrointestinal tract. Furtherpreferably, the measuring module makes the determination usingtechniques described in the above-cited Textbook of Gastroenterology,Volume II, Chapter 10, which is incorporated herein by reference.Alternatively or additionally, the determination may be made usingchemical means (e.g., a pH sensor) or mechanical sensors.

[0027] For some applications, a signal is applied to the esophagus or tothe lower esophageal sphincter, so as to cause contraction of muscletissue therein, thereby making any further eating difficult oruncomfortable.

[0028] Alternatively or additionally, the ingestion-control signal isconfigured so as to induce a feeling of satiation, preferably but notnecessarily using methods or apparatus described in U.S. patentapplication Ser. No. 09/734,358, entitled, “Acute and chronic electricalsignal therapy for obesity,” filed Dec. 11, 2000, or in U.S. ProvisionalPatent Application No. 60/259,925, entitled, “Regulation of eatinghabits,” filed Jan. 5, 2001, both of which are assigned to the assigneeof the present patent application and incorporated herein by reference.For example, methods described in those applications for engendering afeeling of satiation may be applied in conjunction with embodiments ofthe present invention, such that muscles in the vicinity of stretchreceptors in the stomach are caused to contract, thereby resulting indecreased hunger sensations. Alternatively or additionally, the feelingof satiation is induced by applying electrical signals which enhance themobility of chyme from the fundus to the antru=of the stomach, wherestretch-receptor signals are generally generated to a greater extent fora given quantity of food than in the fundus.

[0029] Preferably, the schedule of allowed food ingestion can bemodified after implantation of the apparatus, typically by means of awireless communications link. In this manner, the schedule can beadjusted in response to changes in the patient's eating habits andexperience with the apparatus.

[0030] There is therefore provided, in accordance with a preferredembodiment of the present invention, a method for treating a subject,including:

[0031] receiving a sensor signal responsive to the subject eating;

[0032] analyzing the sensor signal; and

[0033] driving a current into tissue of the subject responsive toanalyzing the signal.

[0034] Typically, receiving the sensor signal includes sensing anelectrical potential change generated responsive to contraction of amuscle of the subject. In addition, analyzing the sensor signal mayinclude identifying a change in a measure of electrical impedancebetween two sites of the muscle. Alternatively or additionally,analyzing the sensor signal may include identifying a change in afrequency component of the electrical potential, e.g., a frequencycomponent which is in the range of approximately 2-7 cycles per minute.

[0035] For some applications, receiving the sensor signal includesmeasuring a change in a physical disposition of a muscle of the subject,or measuring a change in a chemical constituent of the subject.

[0036] In a preferred embodiment, receiving the sensor signal includesreceiving a signal generated in response to a measurement made at anesophageal site of the subject. Alternatively or additionally, receivingthe sensor signal includes receiving a signal generated in response to ameasurement made in a vicinity of a stomach of the subject For someapplications, receiving the sensor signal includes measuring swallowingof the subject.

[0037] In a preferred embodiment, driving the current includes driving acurrent into aural tissue of the subject.

[0038] Typically, driving the current includes driving a current intotissue of a gastrointestinal tract of the subject, e.g., into tissue ofa stomach of the subject For example, driving the current may includedriving the current into a cardiac site of the stomach, a fundic site ofthe stomach, a site in a body of the stomach, a distal site of thestomach, a pyloric site of the stomach, and/or an antral site of thestomach. A “cardiac site of the stomach” refers to a site in closeproximity to the esophageal opening of the stomach.

[0039] For some applications, receiving the sensor signal includesmeasuring an indication of a quantity of ingesta ingested by thesubject, and analyzing the sensor signal includes analyzing the sensorsignal responsive to the quantity.

[0040] Alternatively or additionally, analyzing the sensor signalincludes analyzing the sensor signal responsive to a time of ingestion.For example, analyzing the sensor signal responsive to the time ofingestion may include determining a level of compliance of the subjectwith an ingestion schedule. Determining the level of compliancetypically includes counting a number of meals consumed by the subjectduring a designated time period, and/or counting a number of times thatthe subject swallows food. If appropriate, analyzing the sensor signalmay additionally include receiving a modification to the ingestionschedule, and analyzing the sensor signal responsive to the modifiedingestion schedule. In this latter case, receiving the modification tothe ingestion schedule preferably includes receiving the modification bywireless communication from a source outside of the body of the subject.

[0041] Driving the current preferably includes applying anExcitable-Tissue Control (ETC) signal to the tissue, applying a fencingsignal to the tissue, and/or applying excitatory pulses to the tissue.In a preferred embodiment, the method includes applying a stimulatorypulse at a site of application of the ETC signal. Alternatively oradditionally, the method includes applying a stimulatory pulse to tissueat a site other than a site of application of the ETC signal.

[0042] For some applications, applying the ETC signal includes detectingnatural gastric electrical activity and applying the ETC signalresponsive thereto. For example, detecting the natural gastricelectrical activity may include detecting the natural gastric electricalactivity at a gastric site, and applying the ETC signal may includeapplying the ETC signal at the same gastric site. Alternatively oradditionally, detecting the natural gastric electrical activity includesdetecting at a first site, and applying the ETC signal includes applyingthe ETC signal at a second site, different from the first site. In thislatter case, applying the ETC signal at the second site preferablyincludes timing the application of the ETC signal at the second siteresponsive to a distance between the first and second sites.

[0043] For some applications, driving the current includes:

[0044] driving the current into muscle tissue of the subject; and

[0045] configuring a parameter of the current such that application ofthe current to the muscle tissue causes an increase in an aspect ofcontraction of the muscle tissue.

[0046] In this case, driving the current typically includes driving thecurrent into muscle tissue of a stomach of the subject, and configuringthe parameter includes configuring the parameter such that applicationof the current to the stomach muscle tissue causes tissue contraction ina first portion of the stomach, and, in conjunction with the subjecteating, stretching of a stretch receptor of the stomach in a secondportion of the stomach. Alternatively or additionally, driving thecurrent includes driving the current into muscle tissue of a stomach ofthe subject, and configuring the parameter includes configuring theparameter such that application of the current to the stomach muscletissue enhances movement of chyme from a fundus to an antrum of thestomach.

[0047] Configuring the parameter typically includes configuring theparameter such that application of the current to the muscle tissueinduces a sensation of satiation, discomfort, nausea, and/or vertigo ofthe subject. Alternatively or additionally, driving the current includesconfiguring a parameter of the current such that application of thecurrent causes gastric dysrhytmia of the subject. Further alternativelyor additionally, driving the current includes configuring a parameter ofthe current such that application of the current disrupts coupling ofgastric mechanical activity and gastric electrical activity of thesubject.

[0048] There is also provided, in accordance with a preferred embodimentof the present invention, apparatus for treating a subject, including:

[0049] at least one sensor, adapted to generate a sensor signalresponsive to the subject eating;

[0050] a set of one or more electrodes, adapted to be coupled to tissueof the subject; and

[0051] a control unit, adapted to receive the sensor signal, and todrive a current, responsive to analysis of the signal, through the setof electrodes into the tissue.

[0052] Preferably, the sensor includes at least one of the electrodes.Alternatively or additionally, the sensor includes a mechanical sensoror at least one sensing electrode. In a preferred embodiment, the sensorincludes two sensing electrodes, adapted to be coupled to respectivesites of the tissue, and the control unit is adapted to identify achange in a measure of electrical impedance between two sites of thetissue, and to drive the current responsive to identifying the change.Alternatively or additionally, the control unit is adapted to identify achange in a frequency component of a sensed current flowing through thesensing electrode, and to drive a driving current through the set ofelectrodes responsive to identifying the change in the frequencycomponent of the sensed current.

[0053] In a preferred embodiment, the control unit includes a memory,adapted to store an ingestion schedule, and the control unit is adaptedto withhold driving the current when the sensor signal is indicative ofthe subject eating in accordance with the ingestion schedule.

[0054] For some applications, the apparatus includes an operator unit,which is adapted to be placed external to the subject and to transmit acontrol signal to the control unit, wherein the control unit is adaptedto analyze the sensor signal responsive to the control signal and todrive the current responsive to analyzing the sensor signal.

[0055] The present invention will be more fully understood from thefollowing detailed description of the preferred embodiments thereof,taken together with the drawings, in which:

BRIEF DESCRIPTION OF THE DRAWINGS

[0056]FIG. 1 is a schematic illustration of apparatus for treatingobesity, in accordance with a preferred embodiment of the presentinvention;

[0057]FIG. 2 is a schematic block diagram showing a control unit of theapparatus of FIG. 1, in accordance with a preferred embodiment of thepresent invention;

[0058]FIG. 3 is a flow chart showing an algorithm for controlling theapparatus of FIG. 1, in accordance with a preferred embodiment of thepresent invention;

[0059]FIG. 4A is a graph showing electrical activity of the stomach of apig, in response to an imposed intra-gastric pressure change;

[0060]FIG. 4B is a graph illustrating details of the electrical activityshown in FIG. 4A;

[0061]FIG. 5A is a graph showing baseline strain and pressuremeasurements in the stomach of a pig;

[0062]FIG. 5B is a graph showing strain and pressure measurements in thestomach of a pig, in response to application of an Excitable-TissueControl (ETC) signal thereto, in accordance with a preferred embodimentof the present invention;

[0063]FIG. 6 is a graph showing strain and pressure measurements in arabbit stomach, in response to application of an ETC signal thereto, inaccordance with a preferred embodiment of the present invention;

[0064]FIG. 7 is a graph showing strain measurements in the stomach of ananesthetized pig, in response to application of an ETC signal thereto,in accordance with a preferred embodiment of the present invention;

[0065]FIG. 8 is a graph showing strain measurements in the stomach of ananesthetized pig, in response to application of a fencing signalthereto, in accordance with a preferred embodiment of the presentinvention;

[0066]FIGS. 9 and 10 are graphs showing strain and voltage measurementsin the stomach of an anesthetized pig, before (FIG. 9) and during (FIG.10) application of a fencing signal thereto, in accordance with apreferred embodiment of the present invention;

[0067]FIG. 11 is a graph showing measurements in the stomach of a dog,prior to and during food intake, measured in accordance with a preferredembodiment of the present invention;

[0068]FIG. 12 is a graph showing measurements in the stomach of a dog,during and following food intake, measured in accordance with apreferred embodiment of the present invention;

[0069]FIG. 13 is a graph showing strain measurements in the stomach ofan awake dog, prior to and during application of an ETC signal, inaccordance with a preferred embodiment of the present invention;

[0070]FIG. 14 is a graph showing changes in the weight of a dog during aten-week experimental period, in accordance with a preferred embodimentof the present invention; and

[0071]FIG. 15 is a graph showing frequency changes in a recordedelectrical signal from the antrum of a dog, in accordance with apreferred embodiment of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0072]FIG. 1 is a schematic illustration of diet regulation apparatus18, which detects when a patient eats a meal, and determines, based onthe detection, whether to apply electrical energy to modify the activityof tissue of the patient, in accordance with a preferred embodiment ofthe present invention. Apparatus 18 typically comprises mechanicalsensors 70, supplemental sensors 72, local sense electrodes 74, operatorcontrols 71, and one or more electrodes 100.

[0073] Electrodes 100 are typically coupled to the serosal layer of thestomach and/or inserted into the muscular layer of the stomach.Alternatively or additionally, the electrodes are coupled elsewhere onthe stomach, gastrointestinal tract, or to other suitable locations inor on the patient's body. The number of electrodes and sensors, as wellas the positions thereof, are shown in FIG. 1 by way of example, andother sites on stomach 20 or in or on the patient's body are appropriatefor electrode and sensor placement in other applications of the presentinvention. Different types of electrodes known in the art are typicallyselected based on the specific condition of the patient's disorder, andmay comprise stitch, coil, screw, patch, basket, needle and/or wireelectrodes, or substantially any other electrode known in the art ofelectrical stimulation or sensing in tissue.

[0074] Preferably, apparatus 18 is implanted in the patient in a mannergenerally similar to that used to implant gastric pacemakers or otherapparatus for stimulating the gastrointestinal tract which are known inthe art. As appropriate, techniques described in one or more of thepatents and patent publications cited in the Background section of thepresent patent application may be adapted for use with these embodimentsof the present invention.

[0075]FIG. 2 is a schematic block diagram illustrating details ofoperation of a control unit 90 of apparatus 18, in accordance with apreferred embodiment of the present invention. Preferably, control unit90 is implanted in the patient, and receives signals from mechanicalsensors 70, supplemental sensors 72, and local sense electrodes 74,which are typically implanted on the gastrointestinal tract of thepatient or elsewhere on or in the body of the patient. These sensors andelectrodes are preferably adapted to provide an “ingestion activityanalysis” block 80 of the control unit with information about foodingestion and/or the present state of the stomach.

[0076] Preferably, block 80 determines each time that the patientswallows food, or each time that the patient's stomach begins tocontract in response to a threshold level of ingested food. For example,local sense electrodes 74 may send signals indicative of contraction ofthe esophagus or of the stomach, such that block 80 may process thesignals to determine whether eating has occurred. Alternatively oradditionally, block 80 may filter and process the output of mechanicalsensors 70 situated in the esophagus or in the stomach, so as toidentify mechanical activity of the gastrointestinal tract indicative ofeating. Further alternatively or additionally, block 80 may process datafrom supplemental sensors 72 concerning the blood sugar level of thepatient, to enable an evaluation of whether food has been ingested. (Itis to be understood in the context of the present patent application andin the claims that the terms “food” and “eating” apply equally to“liquids” and “dnnng.”)

[0077] Block 80 typically conveys results of its analysis of the inputsfrom mechanical sensors 70, supplemental sensors 72, and local senseelectrodes 74, to a “parameter search and tuning” block 84 of controlunit 90. Block 84 preferably evaluates the analysis performed by block80 with respect to a pre-programmed or variable ingestion schedulestored in a memory block 88 of control unit 90, so as to determinewhether the patient is in compliance with the schedule. If it isdetermined that the patient's eating is not in compliance with theschedule (e.g., the patient has eaten too much at one meal, or has eatentoo many meals in a day), then block 84 preferably actuates a signalgenerator block 86 to generate electrical signals that are applied byelectrodes 100 to tissue of the patient. Block 86 preferably comprisesamplifiers, isolation units, and other standard circuitry known in theart of electrical signal generation.

[0078] The signals generated by block 86 are preferably configured so asto induce a response appropriate for controlling the patient's eatinghabits. For example, block 86 may drive electrodes 100 to apply signalsto the stomach which induce gastric dysrhythmia and the resultantfeeling of discomfort or nausea. Alternatively or additionally, thesignals are applied to an aural site of the patient (e.g., in a vicinityof the cochlear nerve or the tympanic membrane), and are configured toinduce vertigo, or another unpleasant balance-related sensation.

[0079] For some applications, control unit 90 drives electrodes 100 toapply a modulation signal to muscle in one area of stomach 20, so as toinduce a contraction and/or enhance a spontaneous contraction of thestimulated muscle which, in turn induces satiety, e.g., when food in anadjacent area of the stomach causes additional stretching and/or“pinching” (local, high-intensity contraction) of stretch-receptorstherein. This signal may be applied in addition to or instead of thesignals described hereinabove which produce gastric or other discomfort.The form of contraction-mediated stretching utilized in theseapplications simulates the normal appetite-reduction action of thestomach's stretch-receptors, without the patient having eaten thequantities of food which would normally be required to trigger tisappetite-reduction response.

[0080] Preferably, the signals applied by electrodes 100 include, asappropriate, an Excitable-Tissue Control (ETC) signal and/or anexcitatory signal and/or a fencing signal, so as to induce, modulate,enhance, or inhibit contraction of muscles of the stomach. Aspects ofETC signal application are typically performed in accordance withtechniques described in the above-referenced PCT Publications WO99/03533 and WO 97/25098 and their corresponding U.S. national phaseapplication Ser. Nos. 09/481,253 and 09/101,723, mutatis mutandis. It isnoted that for many applications, it is advantageous to apply thevarious types of signals to the stomach in combination, e.g., to applyan ETC signal and pacing pulses intermittently at the same site, or toapply an ETC signal, an excitatory signal, and a fencing signal atdifferent sites of the stomach, in order to induce sensations which arenot conducive to further eating. Alternatively or additionally, an ETCsignal may be applied to a site on the stomach shortly after anartificial stimulatory (e.g., pacing) pulse is applied at or near thesite, and not in response to detected natural gastric electricalactivity.

[0081] Preferably, regulation apparatus 18 includes remote operatorcontrols 71, external to the patient's body. This remote unit istypically configured to enable the patient or his physician to changeparameters of the ingestion schedule stored in memory block 88. Forexample, if the patient has lost weight, the physician may change theingestion schedule to allow a single mid-afternoon snack Alternativelyor additionally, operator controls 71 comprise an override button, sothat the patient may eat outside of the designated meal times, if theneed arises. Operator controls 71 preferably communicate with controlunit 90 using standard methods known in the art, such as magneticinduction or radio frequency signals.

[0082]FIG. 3 shows a sample algorithm for controlling apparatus 18, inaccordance with a preferred embodiment of the present invention. In thisalgorithm, the criteria for deciding when to apply the signal whichcauses the patient discomfort or nausea are based on detecting when thepatient swallows food. It will be understood by one skilled in the art,having read the disclosure of the present patent application, however,that other suitable techniques may similarly be applied in order todetermine patient compliance with an ingestion schedule. For example,detecting swallowing may be replaced or supplemented by detectingchanges in gastric electrical or mechanical activity.

[0083] Pre-programmed parameters utilized by control unit 90 in thisillustration include the number of allowed meals per day, the number ofswallows that define a meal, and the minimum time duration betweenmeals. The steps in the algorithm are seen to be configured such that ifeither: (a) the number of swallows per meal exceeds that permitted bythe pre-programmed schedule, or (b) the number of meals eaten during aday exceeds the allowed number, then a signal will be applied for afixed duration to electrodes 100, as described hereinabove. It is notedthat in addition to the function described above, the variable“time_between_meals” can be set to a relatively low value, e.g., 30minutes, and thereby allow the patient to swallow food less frequentlythan once every 30 minutes without having this increase theswallow_counter variable.

[0084] It is to be appreciated that whereas the algorithm shown in FIG.3 places emphasis on monitoring patient swallows, this is by way ofillustration and not limitation. For other applications, swallowing isnot monitored, or is only monitored as an adjunct to electrical,mechanical, or chemical monitoring performed by sensors in or on thepatient's stomach, or elsewhere in or on the patient's body. In apreferred embodiment, the onset of eating or drinking is detected onlyby monitoring electrical changes (e.g., electrical impedance changes)via electrodes implanted in or on the patient's stomach.

[0085] Reference is now made to FIGS. 4A and 4B, which are graphsshowing the results of an experiment in which a balloon catheterintroduced into the stomach of a pig was inflated so as to increaseintra-gastric pressure, while the electrical activity of the stomach wascontinuously measured. FIG. 4B shows a portion of the data from FIG. 4A,magnified along the time axis.

[0086] In this experiment, baseline pressure data were recorded by atransducer within the balloon, and gastric electrical activity wassimultaneously monitored by sense electrodes placed at two sites on thestomach. During this baseline period, the stomach is seen to berelatively quiet, with Electrical Control Activity (ECA) being present,but without any Electrical Response Activity (ERA). After about 4minutes, the balloon was inflated, thereby inducing a series of gastriccontractions, which are detectable directly in the upper graph of FIG.4A (pressure), as well as by the frequent ERA seen in the two lowergraphs. These results show that changes in electrical activity of thestomach in response to changes in intra-gastric pressure are measurable.In particular, it is seen that the change in intra-gastric pressure of afew mmHg results in a significant morphological change in the measuredelectrical activity, which can be detected automatically using signalprocessing techniques known in the art. Preferably, analysis of gastricelectrical activity using these techniques is applied to enableautomated detection of the changes in intra-gastric pressure resultingfrom the patient eating.

[0087] Reference is now made to FIGS. 5A, 5B, and 6. FIG. 5A is a graphshowing experimental baseline strain and pressure measurements in thestomach of a pig. FIG. 5B is a graph showing strain and pressuremeasurements in the stomach of the same pig, in response to applicationof an Excitable-Tissue Control (ETC) signal thereto, in accordance witha preferred embodiment of the present invention. FIG. 6 is a graphshowing experimental strain and pressure measurements in a rabbitstomach during a baseline period lasting several minutes and duringseveral minutes of ETC signal application, in accordance with apreferred embodiment of the present invention.

[0088] The results shown in FIGS. 5B and 6 demonstrate that theapplication of ETC signals into gastric muscle tissue causes significantincreases in wall strain (due to contraction), and correspondingincreases in intra-gastric pressure. It is to be understood thatapplication of ETC signals, as part of the ingestion-control signaldescribed hereinabove, is preferred in accordance with some preferredembodiments of the invention. Alternatively or additionally, anothersignal, e.g., one including pacing pulses or a fencing signal, may beapplied so as to induce a sense of patient discomfort or satiety.

[0089]FIG. 7 is a graph showing strain measurements in a pig stomach, inresponse to application of an ETC signal thereto, in accordance with apreferred embodiment of the present invention. In this experiment, ETCsignals were applied for approximately 16 minutes, during which time itis seen that strain generated by muscles of the stomach increasedsignificantly in response to the ETC signals. Removal of the ETC signalsis seen to be associated with a gradual return of the measured values tobaseline levels. The ETC signals were applied as a pulse train,immediately following detected gastric electrical activity. In general,a pulse train frequency of approximately 40-120 Hz is believed to beparticularly suitable, and in this experiment the frequency wasapproximately 80 Hz. The duration of ETC pulse trains (or DC signals) isgenerally optimal if between approximately 500 and 2500 ms, and theduration of the ETC pulse trains in the experiment shown in FIG. 8 wastypically approximately 1500 ms. Peak-to-peak ETC signal amplitudesbetween approximately +/−6 mA and +/−16 mA, typically from +/−8 mA to+/−12 mA were applied to animals in various experiments, including thatshown in FIG. 7. Suitable signal amplitude ranges were found to beparticular for each animal, and, in clinical use, it is recommended butnot required to calibrate the signal amplitude for each patient It isnoted that two ETC signal protocols have been found particularly useful.In the first, sensing of gastric electrical activity at a site isessentially immediately followed by ETC signal application thereto. Inthe second protocol, sensing is performed at a proximal (upstream) site,and an ETC signal is applied to a distal (downstream) site at the timewhen it is estimated that the natural gastric electrical activity sensedat the proximal site will have propagated to the distal site. This timedelay is calculated by dividing the distance between the sensing andsignal-application electrodes by the estimated propagation velocity ofthe natural gastric electrical activity. In either protocol, it may besuitable to apply an additional delay, after the gastric electricalactivity has initiated at a site, before applying the ETC signalthereto.

[0090]FIG. 8 is a graph showing strain measurements in a pig stomach, inresponse to application of a fencing signal thereto, in accordance witha preferred embodiment of the present invention. Preferred methods andapparatus for applying fencing signals for some applications of thepresent invention are described in the above-cited PCT PatentPublication WO 98/10830 to Ben-Haim et al., entitled, “Fencing ofcardiac muscles,” and in U.S. patent application Ser. No. 09/254,903.

[0091] In the experiment whose results are shown in FIG. 8 of thepresent patent application, a DC fencing signal was applied to thestomach between two electrodes placed thereon. During an approximatelyseven minute signal application period, and for approximately sixminutes thereafter, a reduction or modification is seen in mechanicalactivity. Preferred fencing signal applications parameters include a DCsignal having an amplitude of about 0.5 mA-3 mA, and in this experimentthe fencing signal was approximately 1 mA. The duration of applicationof the fencing signal is preferably between about 30 and 90 seconds. Ithas been observed that it is sometimes advantageous to provide shortbreaks during the application of the fencing signal, e.g., once every 30seconds, in order to allow the electrodes to discharge.

[0092] It is expected that when analogous stimulation protocols areapplied in humans, mutatis mutandis, such a reduction or modification ofgastric activity will produce varying levels of discomfort or nausea. Itis noted that whereas it is known in the art that when patientsexperience nausea, there is commonly associated therewith a reduction ofgastric electrical activity (particularly a reduction in the rate ofslow wave generation), the prior art does not teach the deliberatereduction of gastric activity so as to induce nausea. In otherexperiments (not shown), it was found that the polarity of the appliedfencing signal can be modified so as to affect the response of themuscle tissue.

[0093]FIGS. 9 and 10 are graphs showing strain and voltage measurementsin a pig stomach, before and during application of a fencing signalthereto, in accordance with a preferred embodiment of the presentinvention. It is noted that whereas prior to applying the fencing signalthe gastric electrical and mechanical activity recorded are coordinatedand substantial (FIG. 9), during the fencing signal, the recordedelectrical and mechanical activity are reduced essentially to onlynoise. Advantageously, application of the fencing signal (or anothersignal) can be used in order to disturb the coupling between themechanical activity and electrical activity of the stomach, and therebyinduce a feeling in the subject which is not conducive to furthereating.

[0094]FIG. 11 is a graph showing the correlation between measuredelectrical and mechanical activity in the antral portion of the stomachof a dog, prior to and during food intake, measured in accordance with apreferred embodiment of the present invention. Impedance measurementswere performed using electrodes placed 2-3 cm apart on the stomach,while electrical voltage sensing was performed between two electrodesplaced several millimeters apart on the stomach. It is seen thatpeak-to-peak impedance increases with increasing distension of thestomach, and that some frequency components of the sensed voltage (topgraph) and the impedance (middle graph) decrease for at least 15 minutesfollowing the onset of eating.

[0095]FIG. 12 is a graph showing measurements made during and followingfood intake in the stomach of the same animal as in FIG. 11, and shortlyafter the experiment whose results are shown in FIG. 11, measured inaccordance with a preferred embodiment of the present invention. It isnoted that gastric mechanical and electrical activity continues, to asmaller extent, and that it can be measured, as is to be expected, evenafter the discontinuation of food intake at about 3400 seconds.

[0096]FIG. 13 is a graph showing strain measurements in the stomach ofan awake dog, recorded in accordance with a preferred embodiment of thepresent invention. The data were obtained following eating, while foodwas still in the dog's stomach. During the first 200 seconds of thedisplayed data, regular, relatively low magnitude gastric activity isseen in the strain gauge measurements. At approximately T=550 seconds,an ETC signal was applied, and was configured such that each time anonset of natural electrical activity was detected via one of the senseelectrodes (indicating the onset of a contraction), a pulse wasadministered through the sense electrodes. It is seen that the ETCsignal application caused a substantial increase in the magnitude of themeasured contractions. For clinical purposes, similar ETC signals may beapplied after detecting gastric electric activity.

[0097]FIG. 14 is a graph showing changes in the weight of a dog during aseven-week experimental period, which was initiated one week after theimplantation of electrodes on the dog's stomach, as describedhereinabove, in accordance with a preferred embodiment of the presentinvention. Throughout the experiment, the dog was free to eat adlibitum. Daily weight measurements were performed, and the results priorto and during a test period are shown. During an initial 10 day controlperiod, the dog's weight from days 4-10 is seen to be a stable 21 kg.Thereafter, an ETC signal was applied, and was similar to that appliedas described hereinabove with reference to FIG. 7.

[0098] The results of this experiment clearly demonstrate thatapplication of ETC as described herein generates a gradual butsignificant weight loss. In particular, during the 34 days of ETC signalapplication (from day 11 to day 44), the dog showed a maximal weightloss of 7% (1.5 kg from 21 kg). The dog maintained a generally lowweight for two weeks, from day 28 to day 43.

[0099]FIG. 15 is a graph showing calculated frequency changes in anelectrical signal recorded from the antrum of a dog during a meal,recorded and analyzed in accordance with a preferred embodiment of thepresent invention. Three periods are shown, and are based onobservations of when the animal was eating. During Period A, eating hadnot yet commenced, and the frequency of the sensed signal is seen to begenerally stable (in the range of 5-6 cycles per minute). During PeriodB, the animal was fed a measured “pre-load” of 100 grams of food, andthis eating is seen to immediately precede a rapid and significant dropin the measured frequency of the electrical signal, which slowly andpartially recovered during the following 15 minutes. At this point, theanimal was allowed to eat ad libitum, and was seen by observers to eatin four bursts, collectively labeled Period C. The initiation of PeriodC is characterized, like the initiation of Period B, by a sharp drop inmeasured signal frequency. During an approximately 3 minute rest periodbetween the second and third burst of Period C, the frequency of theelectrical signal was seen again to increase.

[0100] It is to be understood that methods and apparatus describedhereinabove may be used advantageously in combination with drugtreatments or in combination with other therapies designed to treatobesity and/or facilitate greater patient control of eating habits.

[0101] It will be appreciated by persons skilled in the art that thepresent invention is not limited to what has been particularly shown anddescribed hereinabove. Rather, the scope of the present inventionincludes both combinations and subcombinations of the various featuresdescribed hereinabove, as well as variations and modifications thereofthat are not in the prior art, which would occur to persons skilled inthe art upon reading the foregoing description.

1. A method for treating a subject, comprising: receiving a sensorsignal responsive to the subject eating; analyzing the sensor signal;and driving a current into tissue of the subject responsive to analyzingthe signal.
 2. A method according to claim 1, wherein receiving thesensor signal comprises measuring a change in a physical disposition ofa muscle of the subject.
 3. A method according to claim 1, whereinreceiving the sensor signal comprises measuring a change in a chemicalconstituent of the subject.
 4. A method according to claim 1, whereinreceiving the sensor signal comprises receiving a signal generated inresponse to a measurement made at an esophageal site of the subject. 5.A method according to claim 1, wherein receiving the sensor signalcomprises receiving a signal generated in response to a measurement madein a vicinity of a stomach of the subject.
 6. A method according toclaim 1, wherein receiving the sensor signal comprises measuringswallowing of the subject.
 7. A method according to claim 1, whereindriving the current comprises driving a current into aural tissue of thesubject.
 8. A method according to claim 1, wherein receiving the sensorsignal comprises measuring an indication of a quantity of ingestaingested by the subject, and wherein analyzing the sensor signalcomprises analyzing the sensor signal responsive to the quantity.
 9. Amethod according to claim 1, wherein driving the current comprisesapplying a fencing signal to the tissue.
 10. A method according to claim1, wherein driving the current comprises applying excitatory pulses tothe tissue.
 11. A method according to claim 1, wherein driving thecurrent comprises configuring a parameter of the current such thatapplication of the current causes gastric dysrhythmia of the subject.12. A method according to claim 1, wherein driving the current comprisesconfiguring a parameter of the current such that application of thecurrent disrupts coupling of gastric mechanical activity and gastricelectrical activity of the subject.
 13. A method according to claim 1,wherein driving the current comprises configuring a parameter of thecurrent such that application of the current induces a sensation ofdiscomfort in the subject.
 14. A method according to claim 1, whereindriving the current comprises configuring a parameter of the currentsuch that application of the current induces a sensation of nausea inthe subject.
 15. A method according to claim 1, wherein driving thecurrent comprises configuring a parameter of the current such thatapplication of the current induces a sensation of vertigo in thesubject.
 16. A method according to any one of claims 1-15, whereinreceiving the sensor signal comprises sensing an electrical potentialchange generated responsive to contraction of a muscle of the subject.17. A method according to claim 16, wherein analyzing the sensor signalcomprises identifying a change in a measure of electrical impedancebetween two sites of the muscle.
 18. A method according to claim 16,wherein analyzing the sensor signal comprises identifying a change in afrequency component of the electrical potential.
 19. A method accordingto claim 18, wherein identifying the change comprises identifying achange in a frequency component which is in the range of approximately2-7 cycles per minute.
 20. A method according to any one of claims 1-15,wherein driving the current comprises driving a current into tissue of agastrointestinal tract of the subject.
 21. A method according to claim20, wherein driving the current comprises driving the current intotissue of a stomach of the subject.
 22. A method according to claim 21,wherein driving the current comprises driving the current into a cardiacsite of the stomach.
 23. A method according to claim 21, wherein drivingthe current comprises driving the current into a fundic site of thestomach.
 24. A method according to claim 21, wherein driving the currentcomprises driving the current into a site in a body of the stomach. 25.A method according to claim 21, wherein driving the current comprisesdriving the current into a distal site of the stomach.
 26. A methodaccording to claim 25, wherein driving the current comprises driving thecurrent into a pyloric site of the stomach.
 27. A method according toclaim 25, wherein driving the current comprises driving the current intoan antral site of the stomach.
 28. A method according to any one ofclaims 1-15, wherein analyzing the sensor signal comprises analyzing thesensor signal responsive to a time of ingestion.
 29. A method accordingto claim 28, wherein analyzing the sensor signal responsive to the timeof ingestion comprises determining a level of compliance of the subjectwith an ingestion schedule.
 30. A method according to claim 29, whereindetermining the level of compliance comprises counting a number of mealsconsumed by the subject during a designated time period.
 31. A methodaccording to claim 29, wherein determining the level of compliancecomprises counting a number of times that the subject swallows food. 32.A method according to claim 29, wherein analyzing the sensor signalcomprises: receiving a modification to the ingestion schedule; andanalyzing the sensor signal responsive to the modified ingestionschedule.
 33. A method according to claim 32, wherein receiving themodification to the ingestion schedule comprises receiving themodification by wireless communication from a source outside of the bodyof the subject.
 34. A method according to any one of claims 1-15,wherein driving the current comprises applying an Excitable-TissueControl (ETC) signal to the tissue.
 35. A method according to claim 34,and comprising applying a stimulatory pulse at a site of application ofthe ETC signal.
 36. A method according to claim 34, and comprisingapplying a stimulatory pulse to tissue at a site other than a site ofapplication of the ETC signal.
 37. A method according to claim 34,wherein applying the ETC signal comprises detecting natural gastricelectrical activity and applying the ETC signal responsive thereto. 38.A method according to claim 37, wherein detecting the natural gastricelectrical activity comprises detecting the natural gastric electricalactivity at a gastric site, and wherein applying the ETC signalcomprises applying the ETC signal at the same gastric site.
 39. A methodaccording to claim 37, wherein detecting the natural gastric electricalactivity comprises detecting at a first site, and wherein applying theETC signal comprises applying the ETC signal at a second site, differentfrom the first site.
 40. A method according to claim 39, whereinapplying the ETC signal at the second site comprises timing theapplication of the ETC signal at the second site responsive to adistance between the first and second sites.
 41. A method according toany one of claims 1-15, wherein driving the current comprises: drivingthe current into muscle tissue of the subject; and configuring aparameter of the current such that application of the current to themuscle tissue causes an increase in an aspect of contraction of themuscle tissue.
 42. A method according to claim 41, wherein driving thecurrent comprises driving the current into muscle tissue of a stomach ofthe subject, and wherein configuring the parameter comprises configuringthe parameter such that application of the current to the stomach muscletissue causes tissue contraction in a first portion of the stomach, and,in conjunction with the subject eating, stretching of a stretch receptorof the stomach in a second portion of the stomach.
 43. A methodaccording to claim 41, wherein driving the current comprises driving thecurrent into muscle tissue of a stomach of the subject, and whereinconfiguring the parameter comprises configuring the parameter such thatapplication of the current to the stomach muscle tissue enhancesmovement of chyme from a fundus to an antrum of the stomach.
 44. Amethod according to claim 41, wherein configuring the parametercomprises configuring the parameter such that application of the currentto the muscle tissue induces a sensation of satiation of the subject.45. Apparatus for treating a subject, comprising: at least one sensor,adapted to generate a sensor signal responsive to the subject eating; aset of one or more electrodes, adapted to be coupled to tissue of thesubject; and a control unit, adapted to receive the sensor signal, andto drive a current, responsive to analysis of the signal, through theset of electrodes into the tissue.
 46. Apparatus according to claim 45,wherein the sensor comprises at least one of the electrodes. 47.Apparatus according to claim 45, wherein the sensor is adapted to beplaced at an esophageal site of the subject.
 48. Apparatus according toclaim 45, wherein the sensor is adapted to be placed at a site of astomach of the subject.
 49. Apparatus according to claim 45, wherein theelectrode set is adapted to be placed at an aural site of the subject.50. Apparatus according to claim 45, wherein the electrode set isadapted to be placed at an esophageal site of the subject.
 51. Apparatusaccording to claim 45, wherein the sensor comprises a mechanical sensor.52. Apparatus according to claim 45, wherein the sensor is adapted togenerate the sensor signal responsive to a quantity of matter ingestedby the subject.
 53. Apparatus according to claim 45, wherein the sensoris adapted to generate the sensor signal responsive to swallowing by thesubject.
 54. Apparatus according to claim 45, wherein the sensor isadapted to generate the sensor signal responsive to a number of mealsconsumed by the subject.
 55. Apparatus according to claim 45, whereinthe control unit is adapted to drive the current into the tissueresponsive to a time of the subject eating.
 56. Apparatus according toclaim 45, wherein the control unit is adapted to configure the currentsuch that driving the current induces gastric dysrhythmia.
 57. Apparatusaccording to claim 45, wherein the control unit is adapted to configurethe current such that driving the current disrupts coupling of gastricmechanical activity and gastric electrical activity of the subject. 58.Apparatus according to claim 45, wherein the control unit is adapted toconfigure the current such that driving the current induces a sensationof discomfort in the subject.
 59. Apparatus according to claim 45,wherein the control unit is adapted to configure the current such thatdriving the current induces a sensation of nausea in the subject. 60.Apparatus according to claim 45, wherein the control unit is adapted toconfigure the current such that driving the current induces a sensationof vertigo in the subject.
 61. Apparatus according to claim 45, whereinthe control unit comprises a memory, adapted to store an ingestionschedule, and wherein the control unit is adapted to withhold drivingthe current when the sensor signal is indicative of the subject eatingin accordance with the ingestion schedule.
 62. Apparatus according toany one of claims 45-61, wherein the electrode set is adapted to beplaced at a site of a stomach of the subject.
 63. Apparatus according toclaim 62, wherein the electrode set is adapted to be placed at a cardiacsite of the stomach
 64. Apparatus according to claim 62, wherein theelectrode set is adapted to be placed at a fundic site of the stomach.65. Apparatus according to claim 62, wherein the electrode set isadapted to be placed at a site on a body of the stomach.
 66. Apparatusaccording to claim 62, wherein the electrode set is adapted to be placedat a distal site of the stomach.
 67. Apparatus according to claim 66,wherein the electrode set is adapted to be placed at a pyloric site ofthe stomach.
 68. Apparatus according to claim 66, wherein the electrodeset is adapted to be placed at an antral site of the stomach. 69.Apparatus according to any one of claims 45-61, wherein the sensorcomprises a sensing electrode.
 70. Apparatus according to claim 69,wherein the sensor comprises two sensing electrodes, adapted to becoupled to respective sites of the tissue, and wherein the control unitis adapted to identify a change in a measure of electrical impedancebetween two sites of the tissue, and to drive the current responsive toidentifying the change.
 71. Apparatus according to claim 69, wherein thecontrol unit is adapted to identify a change in a frequency component ofan electrical potential in a vicinity of the sensing electrode, and todrive the current through the set of electrodes responsive toidentifying the change in the frequency component of the electricalpotential.
 72. Apparatus according to claim 71, wherein the control unitis adapted to identify the change in a frequency component that is inthe range of approximately 2-7 cycles per minute.
 73. Apparatusaccording to any one of claims 45-61, wherein the control unit isadapted to drive the electrode set to apply an Excitable-Tissue Control(ETC) signal to the tissue.
 74. Apparatus according to claim 73, whereinthe control unit is adapted to drive the electrode set to apply astimulatory pulse at a site of application of the ETC signal. 75.Apparatus according to claim 73, wherein the control unit is adapted todrive the electrode set to apply a stimulatory pulse to tissue at a siteother than a site of application of the ETC signal.
 76. Apparatusaccording to claim 73, wherein the sensor is adapted to generate thesensor signal responsive to natural gastric electrical activity, andwherein the control unit is adapted to drive the electrode set to applythe ETC signal responsive thereto.
 77. Apparatus according to claim 76,wherein the sensor is adapted to generate the sensor signal responsiveto natural gastric electrical activity at a site, and wherein thecontrol unit is adapted to drive the electrode set to apply the ETCsignal at the same site.
 78. Apparatus according to claim 76, whereinthe sensor is adapted to generate the sensor signal responsive tonatural gastric electrical activity at a first site, and wherein thecontrol unit is adapted to drive the electrode set to apply the ETCsignal at a second site, different from the first site.
 79. Apparatusaccording to claim 78, wherein the control unit is adapted to timeapplication of the ETC signal responsive to a distance between the firstand second sites.
 80. Apparatus according to claim 73, wherein thecontrol unit is adapted to drive the electrode set to apply the ETCsignal in order to increase an aspect of contraction of the tissue. 81.Apparatus according to claim 80, wherein the control unit is adapted todrive the electrode set to apply the ETC signal in order to cause tissuecontraction in a first portion of a stomach of the subject, andstretching of a stretch receptor of the stomach in a second portion ofthe stomach.
 82. Apparatus according to claim 73, wherein the controlunit is adapted to drive the electrode set to apply the ETC signal inorder to increase a contraction strength of tissue in a vicinity of astretch receptor of a stomach of the subject, so as to increase asensation of satiation of the subject.
 83. Apparatus according to claim73, wherein the control unit is adapted to drive the electrode set toapply the ETC signal to the tissue so as to enhance movement of chymefrom a fundus to an antrum of a stomach of the subject.
 84. Apparatusaccording to any one of claims 45-61, and comprising an operator unit,which is adapted to be placed external to the subject and to transmit acontrol signal to the control unit, wherein the control unit is adaptedto analyze the sensor signal responsive to the control signal and todrive the current responsive to analyzing the sensor signal. 85.Apparatus according to claim 84, wherein the control unit is adapted towithhold driving the current responsive to the control signal. 86.Apparatus according to claim 84, wherein the control unit is adapted toincrease a level of the current responsive to the control signal. 87.Apparatus according to claim 84, wherein the operator unit is adapted totransmit the control signal using wireless communication.